Corticotrophin-Releasing Hormone Type 1 Receptor Gene (CRHR1) Variants Predict Posttraumatic Stress Disorder Onset and Course in Pediatric Injury Patients

Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, 23298-0126, USA.
Disease markers (Impact Factor: 1.56). 04/2011; 30(2-3):89-99. DOI: 10.3233/DMA-2011-0761
Source: PubMed


Posttraumatic stress disorder (PTSD) is a common and disabling anxiety disorder that may occur in the aftermath of exposure to potentially traumatic life events. PTSD is moderately heritable, but few specific molecular variants accounting for this heritability have been identified. Genes regulating the hypothalamic-pituitary-adrenal (HPA) axis, such as corticotrophin-releasing hormone type 1 receptor gene (CRHR1), have been implicated in traumatic-stress related phenotypes but have yet to be studied in relation to PTSD. The present study sought to examine the relation between 9 single nucleotide polymorphisms (SNPs) in the CRHR1 gene and posttraumatic stress symptoms in a prospective study of pediatric injury patients (n=103) who were first assessed in the acute aftermath of their injury at the hospital. Results indicated that multiple SNPs were associated with acute symptoms at a univariate level, and after correction for multiple testing, rs12944712 was significantly related to acute PTSD symptoms. Longitudinal latent growth curve analyses suggest that rs12944712 is also related to both acute symptom level and trajectory of symptoms over time. The present study adds support for the role of CRHR1 in the stress response following potentially traumatic event exposure in youth. It should be noted that the sample size in this study was small, and therefore statistical power was low; following, results from this study should be considered preliminary. Although results are not definitive, the findings from this study warrant future replication studies on how variation in this gene relates to response to traumatic event exposure in youth.

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Available from: Jordan W Smoller, Feb 13, 2014
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    • "; Maniam, Antoniadis, & Morris, 2014; Nicolaides, Charmandari, Chrousos, & Kino, 2014; Stratakis & Chrousos, 1995; Raison & Miller, 2003; Tsigos & Chrousos, 1994; Young, 1998). PTSD has been associated with a range of changes in HPA axis, including elevated levels of the CRH/CRH type 1 receptor (CRHR1) system (Amstadter et al., 2011; White et al., 2013; Wolf et al., 2013), low cortisol levels (T. Chen, Guo, et al., 2014; Horn, Pietrzak, Corsi-Travali, & Neumeister, 2014; Wahbeh & Oken, 2013; Yehuda, Engel, et al., 2005), and increased sensitivity of GR (Lehrner et al., 2014; Yehuda, Cai, et al., 2009). "
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    • "These HPA axis effects occur, in part, through enhanced sensitivity of the glucocorticoid receptor (GR)-mediated feedback mechanism that suppresses stress-induced cortisol release (van Zuiden et al., 2012). Two small studies reported associations between PTSD and cannabinoid receptor (CNR1) gene variants (NM_016083 and NM_033181; (Lu et al., 2008), and between a SNP in corticotropin-releasing hormone receptor-1 (CRHR1, rs12944712) and PTSD onset in paediatric injury patients (Amstadter et al., 2011). "
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    • "3. CRHR1 (rs12944712; chromosome 17q21): Corticotrophin releasing hormone (CRH) is a hormone involved in regulating the stress response via the hypothalamic-pituitary-adrenal (HPA) axis. Multiple variants in the gene encoding the CRH type 1 receptor (CRHR1) have been associated with depression and anxiety both alone and in interaction with exposure to child abuse and trauma (Bradley et al., 2008; Amstadter et al., 2011). 4. FKBP5 (rs1360780, rs9296158, and rs9470080, chromosome 6p21): FKBP5 encodes a negative regulator of glucocorticoid receptor function. "
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